The Washington University High Resolution NMR Facility is requesting funds to purchase a state- of-the-art replacement console and a high-end technology cold probe for its core 600-MHz NMR instrument. The combination of new console and cold probe will markedly improve signal-to-noise and instrument stability, thus greatly facilitating ongoing biochemistry and biomedical research programs, ultimately impacting human health. This request will modernize the highest field spectrometer of the University-wide NMR Facility that serves 40 separate research groups, spanning departments of Anesthesiology, Biochemistry & Molecular Biophysics, Biology, Biomedical Engineering, Cardiology, Chemistry, Infectious Diseases, Internal Medicine, Neurology, Ophthalmology, Pathology, Pharmacology & Developmental Biology, Physics, and Radiology (Division of Radiation Sciences). The NMR Facility supports and maintains six instruments and is staffed with seasoned PhD-level professionals who are committed to user training and collaborative research. The Facility is in its 28th year of operation, is open and available 24 hours a day, 365 days a year, and is committed to serving its extensive user base. This funding request is prompted by the need to maintain the Facility's capabilities in the face of extraordinary technological advances over the past decade, to reduce instrument down-time and maintenance expense, and importantly, to add an ultra-high-sensitivity cold probe that will enable new experiments and provide experimental efficiencies via significantly enhanced signal sensitivity. The scientific research described in ths proposal spans user groups with longstanding interests in fundamental biological, biochemical, and biomedical research and clinically related health questions. These including research areas directed toward light initiated alterations of DNA structure, the creation of molecular patterns that mimic neural communication networks, understanding markers for the genesis and recognition of cancer, understanding structure and genesis of amyloid precursors, elucidation of tissue damage pathways caused by reactive oxidative molecules, and deciphering the altered metabolism of the diabetic heart as well as metabolism alterations associated with carbohydrate-poor diet. This request is made with a financial matching fund commitment from Washington University in the sum of $195,000.